In line with the NEI National Plan to "develop new approaches in ocular diagnosis and therapy" we have devised and tested a new system for targeted delivery of drugs and dyes to local areas in the eye. The goal of the project is to apply the method to gain further knowledge of the retinal microcirculation in health and disease and to evaluate the potential therapeutic efficacy of targeting drugs to the retina. The instrumentation developed to visualize the microvasculature and measure the circulation will be upgraded to optimize the combination of high rate video imaging and high resolution film imaging. The analysis will be enhanced to improve regional and local blood flow measurements, and the image processing will be refined to provide better assessment of the structural changes in the microvasculature. Experimental studies in primates will focus on issues of direct clinical interest. In each study the relation between local and regional blood circulation will be measured and correlated with the functional structure of the microvasculature. The studies will include: the autoregulation of the retinal microcirculation, the effect of hemodilution, early retinal microcirculatory changes in diabetes, and the effect of laser photocoagulation procedures on the macular circulation. A dedicated drug delivery instrument will be developed to permit prolonged targeted delivery of drugs in the retina. The use of intravascular targeting will be assessed by the delivery of thrombogenic agents to treat tumors and neovascularization. The extravascular delivery of drugs will be optimized and its application will be tested by treating experimental melanoma with chemotherapeutic agents. It is hoped that these studies will open new avenues in the diagnosis and therapy of vision threatening conditions.